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ARTICLE INFO Article history: Received 14 March 2013 Received in revised form 24 May 2013 Accepted 2 July 2013 Keywords: Autoimmune hepatitis Catechin Green tea Single nucleotide polymorphism ABSTRACT A [...]

Background Acute severe ulcerative colitis (ASUC) is a potentially life-threatening disease, and the best option in cases of steroid-refractory disease is still debated. We compared the early- and long-term efficacy and safety of the 2 available "rescue therapies", infliximab (IFX) and cyclosporine (CYS), in this setting. Methods We retrospectively evaluated patients admitted for ASUC and treated with "rescue therapy". The primary endpoint was early colectomy-free survival (30 days) and colectomy-free survival until the end of follow up. The secondary endpoints were predictors of colectomy and long-term maintenance of the treatment strategy over time. Results Of 129 patients admitted, 68 received rescue therapy (47 with IFX), whereas 7 underwent early colectomy (10.3%). At 30 days, fewer patients treated with IFX showed a need for colectomy (8.5% vs. 14.3%) compared to those in the CYS group, though the difference was non-significant (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.10-4.69; P=0.47). No severe side effects due to IFX and CYS were observed. During a mean follow up of 40 months, 23 additional patients (37.7%) underwent colectomy, and the rate was significantly lower in the IFX group (25.6%) than in the CYS group (66.7%) (hazard ratio 0.25, 95%CI 0.10-0.61; P=0.003). Colectomy-free survival was significantly higher in the IFX group than in the CYS group (P=0.018) at 12 months. Conclusions In our setting, the early outcomes of IFX and CYS for ASUC were comparable. IFX was associated with significantly lower colectomy rates during the observation period and had a similar safety profile to CYS. [ABSTRACT FROM AUTHOR]

Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality. [ABSTRACT FROM AUTHOR]

Objectives: To investigate radiological sacroiliac abnormalities in IBD patients without musculoskeletal symptoms and to determine the clinical and familiar differences between IBD patients with and without radiologic sacroiliac joint (SIJ) abnormalities. Subsequently, the patients with x-ray alterations were followed for 3 years in order to assess the onset of chronic inflammatory back pain (IBP)., Methods: 81 patients (55 Crohn-CD- and 26 ulcerative rettocolitis-UC) with remittent and low active IBD, from a tertiary referral centre of Gastroenterology Unit, were studied using SIJ x-rays. Differences in IBD clinical variables (activity and duration of CD and UC, extra-intestinal involvement, treatment with surgery and not, ESR and CRP levels), familiarity (for psoriasis, IBD, spondyloarthritis, coeliac syndrome), between patients with SIJ x-ray findings and without were investigated. Patients with radiological sacroiliac joint abnormalities were followed up clinically for 3 years and the onset of symptoms of chronic (higher than 3 consecutive months) IBP was investigated., Results: 22/81 patients (27.1%) showed radiological SIJ abnormalities at baseline: isolated sclerosis in 17/22 (77.3%) and localised erosions in 12/22 (54.5%). Radiological SIJ involvement did not correlate with IBD clinical and familial variables. All patients were HLA B27 negative. At 3 years, 4/22 patients (18.1%) presented chronic IBP symptoms with bone oedema at MRI., Conclusions: In IBD, occult radiological SIJ alterations might precede the onset of axial symptoms but, in the absence of clinical signs, it is not possible to identify some IBD features or familiar predisposition that might be more frequent when SIJ abnormalities are involved. Clinical follow-up might be useful in these patients for a diagnosis of axial spondyloarthritis onset.

A case of autoimmune liver hepatitis is reported: the onset was triggered by consumption of green tea infusion in a patient taking oral contraceptives and irbesartan. We hypothesize that our patient, carrying genetic variant of hepatic metabolism making her particularly susceptible to oxidative stress, developed an abnormal response to a mild toxic insult, afforded by a combination of agents (oral contraceptives+irbesartan+green tea) that normally would not be able to cause damage. Her particular hepatic metabolism further increased the drugs' concentration, favoring the haptenization of liver proteins, eventually leading to the development of an autoimmune hepatitis., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Crohn's disease (CD) is an inflammatory disease characterized by the activation of the immune system in the gut. Since tumor necrosis factor (TNF-alpha) plays an important role in the initiation and perpetuation of intestinal inflammation in CD, we investigated whether TX 527 [19-nor-14,20-bisepi-23-yne-1,25(OH)(2)D(3)], a Vitamin D analogue, could affect peripheral blood mononuclear cells (PBMC) proliferation and exert an immunosuppressive effect on TNF-alpha production in CD patients, and whether this immunosuppressive action could be mediated by NF-kappaB down-regulation. TX 527 significantly decreased cell proliferation and TNF-alpha levels. On activation, NF-kappaB, rapidly released from its cytoplasmatic inhibitor (IKB-alpha), transmigrates into the nucleus and binds to DNA response elements in gene promoter regions. The activation of NF-kappaB, stimulated by TNF-alpha, and its nuclear translocation together with the degradation of IKB-alpha were blocked by TX 527. At the same time, NF-kappaB protein levels present in cytoplasmic extracts decreased in the presence of TNF-alpha and increased when PBMC were incubated with TX 527. The results of our studies indicate that TX 527 inhibits TNF-alpha mediated effects on PBMC and the activation of NF-kappaB and that its action is mediated by Vitamin D receptor (VDR), which is activated when the cells are stimulated with TX 527.

Objective: Intravenously administered infliximab, a monoclonal antibody directed against tumor necrosis factor-alpha, has been proven to be efficacious in the treatment of fistulas in patients with Crohn's disease. It has recently been suggested that local injections of infliximab might be beneficial as well. The aim of this study was to assess whether infliximab could play an effective role in the local treatment of perianal fistulas in Crohn's disease., Material and Methods: Local infliximab injections were administered to 11 patients suffering from Crohn's disease complicated by perianal disease. Eligible subjects included Crohn's disease patients with single or multiple draining fistulas, regardless of status of luminal disease at baseline. Patients, however, were excluded from the study if they had perianal or rectal complications, such as abscesses or proctitis or if they had previously been treated with infliximab. Twenty-milligram doses of infliximab were injected along the fistula tract and around both orifices at baseline and then every 4 weeks for up to 16 weeks or until complete cessation of drainage. No further doses were administered to patients who did not respond after three injections. Efficacy was measured in terms of response (a reduction in fistula drainage of 50% or more) and remission (complete cessation of fistula drainage for at least 4 weeks). Time to loss of response and health-related quality of life were also evaluated., Results: Overall, 8/11 patients (72.7%) responded to the therapy and 4/11 (36.4%) reached remission, whereas 3/11 patients (27.2%) showed no response. Response or remission was very much dependent on the location of the fistulas, and time to loss of response was generally longer for patients who reached remission compared to patients in response. Changes in health-related quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ), also reflected response or remission, with more marked improvements associated with remission. After a mean 10.5 months' follow-up (range 7-18 months), 6/11 patients (54.5%) are in response and 4/11 patients (36.4%) are in remission. No adverse events have been observed in this cohort of patients., Conclusions: Local injections of infliximab along the fistula tract seem to be an effective and safe treatment of perianal fistulas in Crohn's disease. However, further controlled clinical investigations are warranted.